Neuroimaging in psychedelic drug development: past, present, and future

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Psychedelic therapy (PT) is an emerging treatment paradigm with transdiagnostic potential for various psychiatric disorders.
• Classic serotonergic psychedelics (e.g., psilocybin, LSD) acting on the 5-HT2A receptor are central, alongside other promising substances like ketamine, MDMA, and ibogaine.
• Modern PT development coincides with advanced neuroscientific methods, primarily neuroimaging, offering precise assessment of drug and therapy effects on the brain.

Purpose of the Study:

• To outline major trends in psychedelic therapy research, highlighting the benefits of neuroimaging.
• To identify critical knowledge gaps concerning acute versus long-term drug effects, 5-HT2A receptor activity, and neuroplasticity.
• To propose a future research roadmap utilizing multimodal neuroimaging (PET/MRI) to address these gaps.

Main Methods:

• Review of existing data on psychedelic therapy and neuroimaging trends.
• Identification of key research questions regarding drug effects, receptor binding, and neuroplasticity.
• Proposal for future clinical studies combining Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) with specific ligands (e.g., [11C]Cimbi-36) and neuroplasticity measures.

Main Results:

• Neuroimaging has significantly advanced the understanding and development of psychedelic therapy.
• Significant knowledge gaps remain regarding the relationship between acute drug effects and long-term clinical outcomes, precise 5-HT2A receptor characterization, and impact on neuroplasticity.
• Multimodal PET/MRI studies are proposed to bridge molecular, functional, and clinical aspects of PT.

Conclusions:

• Neuroimaging is instrumental in advancing psychedelic therapy research.
• Future research should focus on multimodal imaging studies to elucidate the mechanisms of action and optimize PT.
• Addressing current knowledge gaps will provide a stronger foundation for the clinical development of psychedelic therapies.